Investigating the Association of Cortisol Hypersensitivity Single Nucleotide Polymorphisms with Metabolic Syndrome

Global obesity rates have nearly tripled since 1975. Obesity puts individuals at an increased risk of type II diabetes, fatty liver disease, obstructive sleep apnea, and many more conditions. Although the WHO defines obesity as a BMI greater than or equal to 30, this unfortunately is only one small piece of the puzzle. There are many subtypes of obesity including imbalances in steroid hormones such as cortisol. Cortisol, commonly known as the body’s stress hormone, possesses the ability to affect various functions throughout the body that extend beyond its role in the stress response. Mediated by the HPA axis, when dysregulation occurs, disorders within the body can arise such as Cushing’s Syndrome (CS), caused by the overproduction of cortisol. A disease that is quite similar to CS is Metabolic Syndrome (MSX). While the presentation of these two diseases may be difficult to differentiate between, people with MSX have normal cortisol levels. This paradox suggests that some other mechanism could be at play that is causing this hypercortisolemia phenotype in the presence of normal cortisol levels for MSX patients. One possible mechanism is that people with MSX might have a hypersensitivity to cortisol. Past research has indicated there have been SNPs, or single nucleotide polymorphisms, found in the genes associated with hypersensitivity to cortisol as well as many genes with known SNPs that play a pivotal role in the regulation and action of cortisol in the body. We hypothesized that the presence of these SNPs leads to a hypersensitivity to cortisol and is associated with the development of MSX. In collaboration with the Ellis Bariatric Care Center, we are collecting buccal DNA swabs from patients with obesity and determining SNP allele frequencies by qPCR. Specific SNPs are showing correlation with individual characteristics of MSX such as elevated triglyceride levels. Identifying genetic markers that are associated with MSX should give physicians the ability to intervene early on to hopefully prevent its further development.